Clinical performance of the Prostate Health Index (PHI) for the prediction of prostate cancer in obese men: data from the PROMEtheuS project, a multicentre European prospective study.

OBJECTIVES: To test serum prostate-specific antigen (PSA) isoform [-2]proPSA (p2PSA), p2PSA/free PSA (%p2PSA) and Prostate Health Index (PHI) accuracy in predicting prostate cancer in obese men and to test whether PHI is more accurate than PSA in predicting prostate cancer in obese patients. PATIENTS AND METHODS: The analysis consisted of a nested case-control study from the pro-PSA Multicentric European Study (PROMEtheuS) project. The study is registered at http://www.controlled-trials.com/ISRCTN04707454. The primary outcome was to test sensitivity, specificity and accuracy (clinical validity) of serum p2PSA, %p2PSA and PHI, in determining prostate cancer at prostate biopsy in obese men [body mass index (BMI) ≥30 kg/m(2) ], compared with total PSA (tPSA), free PSA (fPSA) and fPSA/tPSA ratio (%fPSA). The number of avoidable prostate biopsies (clinical utility) was also assessed. Multivariable logistic regression models were complemented by predictive accuracy analysis and decision-curve analysis. RESULTS: Of the 965 patients, 383 (39.7%) were normal weight (BMI <25 kg/m(2) ), 440 (45.6%) were overweight (BMI 25-29.9 kg/m(2) ) and 142 (14.7%) were obese (BMI ≥30 kg/m(2) ). Among obese patients, prostate cancer was found in 65 patients (45.8%), with a higher percentage of Gleason score ≥7 diseases (67.7%). PSA, p2PSA, %p2PSA and PHI were significantly higher, and %fPSA significantly lower in patients with prostate cancer (P < 0.001). In multivariable logistic regression models, PHI significantly increased accuracy of the base multivariable model by 8.8% (P = 0.007). At a PHI threshold of 35.7, 46 (32.4%) biopsies could have been avoided. CONCLUSION: In obese patients, PHI is significantly more accurate than current tests in predicting prostate cancer.

Clinical performance of serum isoform [-2]proPSA (p2PSA), and its derivatives %p2PSA and the Prostate Health Index, in men aged <60 years: results from a multicentric European study.

OBJECTIVES: To test the hypothesis that [-2]proPSA (p2PSA) and its derivatives are more accurate than total prostate-specific antigen (tPSA), free prostate-specific antigen (fPSA) and fPSA as percentage of tPSA (%fPSA) in detecting prostate cancer (PCa) in men aged <60 years. PATIENTS AND METHODS: The analysis consisted of a nested case-control study from the PRO- PSA Multicentric European Study (PROMEtheuS) project. The primary outcomes were measures of sensibility, specificity and accuracy of serum p2PSA, p2PSA as percentage of fPSA (%p2PSA) and Beckman Coulter prostate health index (PHI) in men aged <60 years who had undergone a prostate biopsy. The potential reduction in the number of unnecessary biopsies and the characteristics of the potentially missed PCa cases were reported as secondary outcomes. Multivariate logistic regression models were complemented by predictive accuracy and decision-curve analyses. RESULTS: Of the 1036 patients enrolled in the PROMEtheus project, 238 (22.9%) were aged < 60 years. PCa was found in 67 subjects (28.1%); p2PSA, %p2PSA and PHI values were significantly higher (P < 0.001) among these subjects, while no differences were found in tPSA, fPSA and %fPSA values. On univariate analysis, %p2PSA (area under the curve [AUC]: 0.704) and PHI (AUC: 0.7) were the most accurate predictors, and these significantly outperformed tPSA (AUC: 0.549), fPSA (AUC: 0.511) and %fPSA (AUC: 0.557) in the prediction of PCa at biopsy (P ≤ 0.001). In multivariate logistic regression models, %p2PSA and PHI achieved independent predictor status and significantly increased the accuracy of multivariate models by 6.3 and 7.6%, respectively (P ≤ 0.05). CONCLUSION: PHI and %p2PSA are more accurate than the reference standard tests in predicting PCa in young men.

Head-to-head comparison of prostate health index and urinary PCA3 for predicting cancer at initial or repeat biopsy.

PURPOSE: We performed a head-to-head comparison of the PHI (Prostate Health Index) and PCA3. MATERIALS AND METHODS: We evaluated PHI and PCA3 performance in 211 patients undergoing initial (116) or repeat (95) prostate biopsy. Multivariable logistic regression analysis was done using the AUC to test the accuracy of PHI and PCA3 for predicting prostate cancer in the overall population and in each setting. Decision curve analysis was used to compare the clinical benefit of different models. RESULTS: Overall, the AUC of the PHI (0.70) was significantly higher than the AUC of PCA3 (0.59), total prostate specific antigen (0.56) and free-to-total prostate specific antigen (0.60) (p = 0.043, 0.002 and 0.037, respectively). PHI was more accurate than PCA3 for predicting prostate cancer in the initial setting (AUC 0.69 vs 0.57) and in the repeat setting (AUC 0.72 vs 0.63), although no statistically significant difference was observed. Including PCA3 in the base multivariable model (prostate specific antigen plus free-to-total prostate specific antigen plus prostate volume) did not increase predictive accuracy in either setting (AUC 0.79 vs 0.80 and 0.75 vs 0.76, respectively). Conversely, including PHI in the base multivariable model improved predictive accuracy by 5% (AUC 0.79 to 0.84) and 6% (AUC 0.75 to 0.81) in the initial and repeat prostate biopsy settings, respectively. On decision curve analysis the highest net benefit was observed when PHI was added to the base multivariable model. CONCLUSIONS: PHI and PCA3 provide a significant increase in sensitivity and specificity compared to all other examined markers and they may help guide biopsy decisions. PCA3 does not increase the accuracy of predicting prostate cancer when PHI is assessed.

Serum index test %[-2]proPSA and Prostate Health Index are more accurate than prostate specific antigen and %fPSA in predicting a positive repeat prostate biopsy.

PURPOSE: We tested the hypothesis that serum isoform [-2]proPSA derivatives %p2PSA and Prostate Health Index are accurate predictors of prostate cancer in men scheduled for repeat biopsy. MATERIALS AND METHODS: The study was an observational prospective evaluation of a clinical cohort of men with 1 or 2 previous negative prostate biopsies, with persistent suspicion of prostate cancer. They were enrolled in the study to determine the diagnostic accuracy of %p2PSA using the formula, (p2PSA pg/ml)/(free prostate specific antigen ng/ml × 1,000)]× 100, and Beckman-Coulter Prostate Health Index using the formula, (p2PSA/free prostate specific antigen) × âˆštotal prostate specific antigen), and to compare it with the accuracy of established prostate cancer serum tests (total prostate specific antigen, free prostate specific antigen and percent free prostate specific antigen). Multivariable logistic regression models were complemented by predictive accuracy analysis and decision curve analysis. RESULTS: Prostate cancer was found in 71 of 222 (31.9%) subjects. %p2PSA and Prostate Health Index were the most accurate predictors of disease. %p2PSA significantly outperformed total prostate specific antigen, free prostate specific antigen, percent free prostate specific antigen and p2PSA in the prediction of prostate cancer (p ≤0.01), but not Prostate Health Index (p = 0.094). Prostate Health Index significantly outperformed total prostate specific antigen and p2PSA (p ≤0.001) but not free prostate specific antigen (p = 0.109) and free/total prostate specific antigen (p = 0.136). In multivariable logistic regression models %p2PSA and Prostate Health Index achieved independent predictor status, and significantly increased the accuracy of multivariable models including prostate specific antigen and prostate volume with or without percent free prostate specific antigen and prostate specific antigen density by 8% to 11% (p ≤0.034). At a %p2PSA cutoff of 1.23, 153 (68.9%) biopsies could have been avoided, missing prostate cancer in 6 patients. At a Prostate Health Index cutoff of 28.8, 116 (52.25%) biopsies could have been avoided, missing prostate cancer in 6 patients. CONCLUSIONS: Serum %p2PSA and Prostate Health Index are more accurate than standard reference tests in predicting repeat prostate biopsy outcome, and could avoid unnecessary repeat biopsies.

Current role of robotic assisted partial nephrectomy.

The modern urologists are nowadays greatly involved in the surgical management of small renal masses, where nephron sparing surgery showed adequate oncological results, with a saving of a great amount of healthy renal tissue. Among the various minimally invasive surgical options, laparoscopic partial nephrectomy duplicates the open technique considered the standard of referral. Robotic assisted partial nephrectomy, aims to add to laparoscopy all the well known advantages offered by the Da Vinci system, such as the 3-Dvision and 7 degree of freedom of surgical instruments. We reviewed the current English literature on robotic partial nephrectomy published in 2008-2009 with at least 20 cases, adding our experience of 26 cases. Although the retroperitoneoscopic approach showed to be feasible in selected cases, all the procedures reported were performed with a transperitoneal approach. Among the 106 robotic assisted partial nephrectomy procedures selected, the mean tumor diameter was 2.8 cm; the mean operative time was 148.7 min with a mean warm ischemia time of 23.8 min and the positive surgical margins rate was 1.8%, reflecting the learning curve of the procedure. Overall complications rate was 15%, although the majority were minor and conservatively treated. Although robotic partial nephrectomy is still in its infancy, it showed adequate overall results when compared to laparoscopic partial nephrectomy with similar results but with a reduced learning curve. Actually robotic partial nephrectomy should be considered a viable option for nephron sparing surgery both in experienced laparoscopy centers for larger lesions in robotic naive centers where it may become the standard option for the treatment of small renal masses.

Current Standard Technique for Modern Flexible Ureteroscopy: Tips and Tricks.

BACKGROUND: Thanks to advancements in the endoscopic armamentarium, flexible ureteroscopy (fURS) has become a viable and attractive option for the treatment of renal stones because of its high stone-free rates (SFRs) and low morbidity. OBJECTIVE: To describe our surgical technique for fURS, step-by-step, for the treatment of renal stones and to assess its effectiveness and safety. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of 316 consecutive patients who underwent fURS for renal stones at our institution between March 2014 and September 2015 was performed. SURGICAL PROCEDURE: Ureteroscopy and laser lithotripsy using a standardized technique with last-generation flexible ureteroscopes. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Clinical data were collected in a dedicated database. Intraoperative and postoperative outcomes were assessed. A descriptive statistical analysis was performed. RESULTS AND LIMITATIONS: The mean overall stone size was 16.5 ± 7.9mm. Ureteral access sheath placement was possible in 287 patients (90.8%). At 1-mo follow-up, the overall primary SFR was 79.1%; the secondary and tertiary SFRs were 89.5% and 91.5%, respectively. The mean operative time was 72.6 ± 27.5min. The mean number of procedures was 1.27. Complications were reported in 92 patients (29.1%) overall, with Clavien grade 1 in 55 patients (17.4%), grade 2 in 30 patients (9.5%), grade 3 in 6 patients (1.9%), grade 4 in 1 patient (0.3%), and grade 5 in none. The main limitation of the study was the retrospective nature. CONCLUSIONS: The fURS procedure is safe and effective for the treatment of renal stones. A staged procedure is necessary to achieve stone-free status with large calculi. PATIENT SUMMARY: Flexible ureteroscopy is an effective treatment with low complication rates for the majority of renal stones. Both the modern highly technological armamentarium and surgical know-how should be available.

Simultaneous Bilateral Endoscopic Manipulation for Bilateral Renal Stones.

OBJECTIVE: To report the first performance of simultaneous bilateral percutaneous nephrolithotomy and flexible ureteroscopy carried out in tandem by 2 different surgeons in a patient with bilateral medium-sized renal calculi, describing step-by-step details of the surgical technique. MATERIALS AND METHODS: A 46-year-old man, affected with hyperparathyroidism, was diagnosed with asymptomatic bilateral medium-sized renal stones. An abdominal noncontrast computed tomography scan revealed a left single kidney stone with a maximum diameter of 16 mm and 2 right renal stones located in the pelvis and in the lower calyx, of 21 and 19 mm in maximum diameter, respectively. A bilateral simultaneous percutaneous nephrolithotomy on the right side and flexible ureteroscopy on the left side were therefore carried out. RESULTS: The total operative time was 80 minutes. No intra- or postoperative complications were experienced. On postoperative day 1, the creatinine serum level was stable (0.7 mg/dL); he was discharged home 48 hours later. Ureteral stents were removed 7 days after the procedure. At 2 weeks follow-up, an abdominal noncontrast computed tomography scan showed a stone-free status and no changes in renal function were detected. CONCLUSION: A simultaneous bilateral endoscopic manipulation is feasible and safe and it can be offered in the presence of medium-sized bilateral renal stones in high-volume centers by experienced surgeons.

Minimally Invasive Partial Nephrectomy Versus Laparoscopic Cryoablation for Patients Newly Diagnosed with a Single Small Renal Mass.

BACKGROUND: Minimally invasive partial nephrectomy (MIPN) and laparoscopic renal cryoablation (LRC) are two treatment options increasingly used for small renal masses. OBJECTIVE: To compare perioperative, oncologic, and functional outcomes after MIPN and LRC. DESIGN, SETTING, AND PARTICIPANTS: We included 372 consecutive patients newly diagnosed with a single small renal mass and treated with either MIPN or LRC at a single institution. INTERVENTION: MIPN and LRC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Regression models were used to evaluate the impact of surgical treatment (MIPN vs LRC) on perioperative, oncologic, and functional outcomes. RESULTS AND LIMITATIONS: Overall, 206 patients (55%) underwent MIPN and 166 (45%) were treated with LRC. In multivariate analysis, the rate of postoperative complications was significantly lower in the MIPN compared to the LRC group (20% vs 28%; adjusted difference -11%; p=0.02) after adjusting for age at surgery, American Society of Anesthesiologists score (1 vs 2 vs 3), and tumor size. The median follow-up was similar in the two groups (43 and 39 mo for MIPN and LRC, respectively). In univariate Cox regression analysis, treatment type was not significantly associated with disease-free survival (hazard ratio 1.06, 95% confidence interval [CI] 0.45-2.52; p=0.9). The disease-free survival rate at 5 yr was 92% in MIPN and 93% in LRC patients. In multivariate linear regression analysis, LRC was significantly associated with a higher estimated glomerular filtration rate (eGFR) at 6 mo compared to MIPN (coefficient 4.68, 95% CI 0.06-9.30; p=0.047) after adjusting for age at surgery, tumor size, and preoperative eGFR. There was no significant association between surgical treatment and postoperative eGFR at 3 yr after surgery (coefficient -2.36, 95% CI -7.55 to 2.83; p=0.4). Limitations include the retrospective study design and selection bias. CONCLUSIONS: MIPN and LRC provided similar cancer control and comparable renal function at intermediate-term follow-up. Both surgical techniques emerged as viable treatment options for patient newly diagnosed with a single small renal mass. Further multi-institutional studies with longer follow-up and nephrometry scores are needed to corroborate our findings. PATIENT SUMMARY: In patients newly diagnosed with a single small renal mass, minimally invasive partial nephrectomy and laparoscopic renal cryoablation provided similar cancer control and comparable renal function at intermediate-term follow-up.

Relationship of chronic histologic prostatic inflammation in biopsy specimens with serum isoform [-2]proPSA (p2PSA), %p2PSA, and prostate health index in men with a total prostate-specific antigen of 4-10 ng/ml and normal digital rectal examination.

OBJECTIVE: To investigate the relationship between serum [-2]proPSA (p2PSA) and derivatives with chronic histologic prostatic inflammation (CHPI) in men undergoing prostate biopsy for suspected prostate cancer (PCa). METHODS: This nested case-control study resulted from an observational prospective trial for the definition of sensibility, specificity, and accuracy of p2PSA, %p2PSA, and Beckman Coulter Prostate Health Index (PHI), in men undergoing prostate biopsy, with a total prostate-specific antigen (PSA) of 4-10 ng/mL and normal digital rectal examination. CHPI was the outcome of interest and defined as the presence of moderate to large infiltration of lymphomononuclear cells with interstitial and/or glandular disruption in absence of PCa. p2PSA, %p2PSA, and PHI were considered the index tests and compared with the established biomarker reference standard tests: tPSA, fPSA, %fPSA. RESULTS: Of 267 patients subjected to prostate biopsy, 73 (27.3%) patients were diagnosed with CHPI. Comparing CHPI with PCa patients, %p2PSA and PHI were found to be significantly lower, whereas fPSA and %fPSA were significantly higher. %p2PSA and PHI were the most accurate predictors of CHPI at biopsy, significantly outperforming tPSA, fPSA, and %fPSA. On the contrary, no significant differences were found in PSA, p2PSA, and derivatives between CHPI and benign prostatic hyperplasia (BPH) patients. CONCLUSION: Our findings showed that p2PSA, %p2PSA, and PHI values might discriminate PCa from CHPI or BPH, but not CHPI from BPH, in men with a total PSA 4-10 ng/mL and normal digital rectal examination. p2PSA isoform and its derivatives could be useful in clinical decision making to avoid unnecessary biopsies in patients with CHPI and elevated tPSA value.

Clinical use of [-2]proPSA (p2PSA) and its derivatives (%p2PSA and Prostate Health Index) for the detection of prostate cancer: a review of the literature.

Prostate-specific antigen (PSA) is recognized as an organ-specific marker with low specificity and sensitivity in discriminating prostate cancer (PCa) from other benign conditions, such as prostatic hyperplasia or chronic prostatitis. Thus, in the case of clinical suspicion, a PCa diagnosis cannot be made without a prostate biopsy. [-2]proPSA (p2PSA), a precursor of PSA, has been investigated as a new marker to accurately detect PCa. The aim of this systematic review was to discuss the available literature regarding the clinical validity and utility of p2PSA and its derivatives, p2PSA/fPSA (%p2PSA) and the Prostate Health Index (PHI). A systematic search of the PubMed and Scopus electronic databases was performed in accordance with the PRISMA statement (http://www.prisma-statement.org), considering the time period from January 1990 to January 2014 and using the following search terms: proprostate specific antigen, proenzyme PSA, proPSA, [-2]proPSA, p2PSA, Prostate Health Index, and PHI. To date, 115 studies have been published, but only 35 were considered for the qualitative analysis. These studies suggested that p2PSA is the most cancer-specific form of PSA, being preferentially expressed in PCa tissue and being significantly elevated in the serum of men with PCa. It is now evident that p2PSA, %p2PSA, and PHI measurements improve the specificity of the available tests (PSA and derivatives) in detecting PCa. Moreover, increasing PHI values seem to correlate with more aggressive disease. Some studies have compared p2PSA and its derivatives with other new biomarkers and found p2PSA to be significantly more accurate. Indeed, the implementation of these tests in clinical practice has the potential to significantly increase the physician's ability to detect PCa and avoid unnecessary biopsies, while also having an effective impact on costs. Further studies in large, multicenter, prospective trials are required to confirm these encouraging results on the clinical utility of these new biomarkers.

Complications and quality of life after template-assisted transperineal prostate biopsy in patients eligible for focal therapy.

OBJECTIVE: To assess the complication rates and quality of life in patients eligible for focal therapy who underwent template-assisted transperineal prostate biopsy (TTPB). MATERIALS AND METHODS: Eighty-seven patients with low-risk prostate cancer (clinical stage T1c-T2a, prostate-specific antigen level ≤10 ng/mL, biopsy Gleason score ≤6), who were candidates for focal therapy, underwent TTPB. The study details are available from http://clinicaltrials.gov (NCT00928603). The primary outcomes were the complication rates, according to the Clavien-Dindo classification, and changes in the quality of life, evaluated using the International Prostate Symptom Score, International Index of Erectile Function, and Functional Assessment of Cancer Therapy-Prostate questionnaires, before and 1 month after TTPB. RESULTS: The median patient age was 63.9 years (range 46-78), with a median Charlson comorbidity index of 2.2 (range 0-4). No statistically significant differences were observed when comparing the general and/or specific domains of the International Prostate Symptom Score, International Index of Erectile Function, and Functional Assessment of Cancer Therapy-Prostate results before and 1 month after TTPB (P >.05 for all). Using the Clavien-Dindo classification, we observed 37 cases of grade 1 complications, including 5 (6.1%) cases of macrohematuria, 13 (16%) of hemospermia, 11 (13.5%) of perineal hematoma, 3 (3.7%) of perineal hematoma and hemospermia, and 5 (6.1%) of macrohematuria and hemospermia. Three patients (3.7%) developed a grade II complication (ie, acute urinary retention). Prostate cancer was detected in 54 patients (62.1%). Of 57 patients, 16 (29.6%) were upgraded from Gleason score 3+3/atypical small acinar proliferation to Gleason score 7. Of the 54 patients with positive TTPB findings, 18 (25.3%) showed an anatomic correspondence between the results of previous biopsies and TTPB. CONCLUSION: TTPB did not appear to have a significant effect on the quality of life of candidates for focal therapy, and the Clavien-Dindo complication rate was negligible.

Preoperative prostate-specific antigen isoform p2PSA and its derivatives, %p2PSA and prostate health index, predict pathologic outcomes in patients undergoing radical prostatectomy for prostate cancer.

BACKGROUND: Currently available predictive models fail to assist clinical decision making in prostate cancer (PCa) patients who are possible candidates for radical prostatectomy (RP). New biomarkers would be welcome. OBJECTIVE: Test the hypothesis that prostate-specific antigen (PSA) isoform p2PSA and its derivates, percentage of p2PSA to free PSA (%p2PSA) and the Prostate Health Index (PHI), predict PCa characteristics at final pathology after RP. DESIGN, SETTING, AND PARTICIPANTS: An observational prospective study was performed in 350 consecutive men diagnosed with clinically localised PCa who underwent RP. MEASUREMENTS: We determined the predictive accuracy of serum total PSA (tPSA), free PSA (fPSA), fPSA-to-tPSA ratio (%fPSA), p2PSA, %p2PSA, and PHI. The primary end point was to determine the accuracy of these biomarkers in predicting the presence of pT3 disease, pathologic Gleason sum≥7, Gleason sum upgrading, and tumour volume<0.5 ml. INTERVENTION: Open retropubic and robot-assisted laparoscopic RP was performed. Pelvic lymphadenectomy was performed according to baseline oncologic parameters and the surgeon's judgement. RESULTS AND LIMITATIONS: The %p2PSA and PHI levels were significantly higher in patients with pT3 disease, pathologic Gleason sum≥7, and Gleason sum upgrading (all p values<0.001). Conversely, %p2PSA and PHI levels were significantly lower in patients with tumour volume<0.5 ml (p<0.001). By univariate analysis, both %p2PSA and PHI were accurate predictors of pT3 disease, pathologic Gleason sum≥7, Gleason sum upgrading, and tumour volume<0.5 ml. By multivariate analyses, the inclusion of both %p2PSA and PHI significantly increased the predictive accuracy of a base multivariate model (excluding the tumour volume prediction for both variables, and Gleason sum upgrading for the model including %p2PSA) that included patient age, tPSA, fPSA, f/tPSA, clinical stage, and biopsy Gleason sum. CONCLUSIONS: We found that p2PSA and its derivatives are predictors of PCa characteristics at final pathology after RP and are more accurate than currently available markers.